2-47466567-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000251.3(MSH2):c.1511-91G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,235,160 control chromosomes in the GnomAD database, including 65,847 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).

Frequency

Genomes: 𝑓 0.40 ( 14050 hom., cov: 33)

Exomes 𝑓: 0.30 ( 51797 hom. )

Consequence

MSH2
NM_000251.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:5

Conservation

PhyloP100: -1.71

Publications

18 publications found

Variant links:

Genes affected

MSH2 (HGNC:7325): (mutS homolog 2) This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

MSH2 Gene-Disease associations (from GenCC):

Lynch syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet
Lynch syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics
Muir-Torre syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P
mismatch repair cancer syndrome 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
mismatch repair cancer syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
ovarian cancer
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
malignant pancreatic neoplasm
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
prostate cancer
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
rhabdomyosarcoma
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
breast cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MSH2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-47466567-G-T is Benign according to our data. Variant chr2-47466567-G-T is described in ClinVar as Benign. ClinVar VariationId is 90689.Status of the report is reviewed_by_expert_panel, 3 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSH2	NM_000251.3 link	c.1511-91G>T		intron_variant	Intron 9 of 15	ENST00000233146.7	NP_000242.1	P43246-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSH2	ENST00000233146.7 link	c.1511-91G>T		intron_variant	Intron 9 of 15	1	NM_000251.3	ENSP00000233146.2		P43246-1

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60638

AN:

151942

Hom.:

14031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.221

Gnomad NFE

AF:

0.277

Gnomad OTH

AF:

0.360

GnomAD4 exome

AF:

0.296

AC:

320283

AN:

1083098

Hom.:

51797

AF XY:

0.295

AC XY:

163294

AN XY:

553690

show subpopulations

African (AFR)

AF:

0.624

AC:

15618

AN:

25020

American (AMR)

AF:

0.297

AC:

12288

AN:

41308

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

5537

AN:

23652

East Asian (EAS)

AF:

0.594

AC:

21034

AN:

35418

South Asian (SAS)

AF:

0.319

AC:

24092

AN:

75510

European-Finnish (FIN)

AF:

0.387

AC:

19884

AN:

51344

Middle Eastern (MID)

AF:

0.243

AC:

1146

AN:

4718

European-Non Finnish (NFE)

AF:

0.264

AC:

205241

AN:

778762

Other (OTH)

AF:

0.326

AC:

15443

AN:

47366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

9966

19932

29897

39863

49829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6016

12032

18048

24064

30080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.399

AC:

60707

AN:

152062

Hom.:

14050

Cov.:

AF XY:

0.402

AC XY:

29884

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.623

AC:

25834

AN:

41484

American (AMR)

AF:

0.340

AC:

5192

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

787

AN:

3468

East Asian (EAS)

AF:

0.636

AC:

3295

AN:

5178

South Asian (SAS)

AF:

0.341

AC:

1646

AN:

4822

European-Finnish (FIN)

AF:

0.389

AC:

4101

AN:

10552

Middle Eastern (MID)

AF:

0.223

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.277

AC:

18816

AN:

67974

Other (OTH)

AF:

0.359

AC:

758

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1685

3369

5054

6738

8423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.324

Hom.:

3553

Bravo

AF:

0.404

Asia WGS

AF:

0.493

AC:

1714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Lynch syndrome 1

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lynch syndrome

Benign:1

Sep 05, 2013

International Society for Gastrointestinal Hereditary Tumours (InSiGHT)

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:research

MAF >1% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.037

(source)

DANN

Benign

0.30

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over